Liver failure is the cause of death of over 30,000 patients in the United States every year and over 2 million patients worldwide. Drug-induced liver disease is a major challenge for the pharmaceutical industry since unforeseen liver toxicity causes many new drug candidates to fail either in clinical trials or after release. In vitro cell culture techniques can be used to study human and animal hepatic tissue cells, and the effects of various drugs on the cells. Additionally, in vitro models can provide valuable information on drug uptake and metabolism, enzyme induction, and drug interactions affecting metabolism and hepatotoxicity. Micropatterned hepatocyte-stromal cell co-culture (MPCC) systems have been developed recently for culturing hepatocytes. One of the remarkable features of the MPCC technology is that for human, rat, and monkey hepatocytes, the cultures remain relatively phenotypically stable for at least a month. This is in contrast to prior technology such as monocultures of hepatocytes that are only stable for a week.
However, application of existing MPCC technology to canine hepatocyte cell culture causes early and extreme morphological changes to the architecture of the cell culture (loss of uniform island shape) and extreme hypertrophy of the hepatocytes. The morphological changes reduce confidence that the canine co-cultures are representative of in-vivo liver tissue. Therefore, the correlation of the existing canine co-culture with in-vivo canine livers is highly questionable. Thus, a need exists for improved canine co-cultures that can serve as reliable models of in-vivo canine livers.